tbuckley/cabot-search huggingface dataset:
Identification of a novel subtype of endometrial cancer with unfavorable outcome using artificial intelligence-based histopathology image analysis.
Authors: Amirali Darbandsari, Hossein Farahani, Purang Abolmaesumi, Samuel Leung, Stefan Kommoss, David Huntsman, Aline Talhouk, C. Blake Gilks, Jessica N. McAlpine, Ali Bashashati
Journal: Journal of Clinical Oncology (2022)

5594 Background: Molecular subtyping of endometrial cancer (EC), unlike histopathological evaluation, offers an objective and reproducible classification system that has strong prognostic value and therapeutic implications. The Proactive Molecular risk classifier for Endometrial cancer (ProMisE) was developed by our team as a pragmatic, cost-effective, and clinically applicable molecular classifier for EC patients. ProMisE has four subtypes: (i) POLE mutant ( POLEmut), (ii) mismatch repair deficient (MMRd), (iii) p53 abnormal (p53abn) by immunohistochemistry, and (iv) NSMP (No Specific Molecular Profile), lacking any of the defining features of the other three subtypes. While ProMisE subtypes are associated with clinical outcomes, within each subtype, there are clinical/prognostic outliers. This is particularly true within the largest ProMisE subtype; NSMP (representing ̃50% of ECs), where a subset of patients experience a very aggressive disease course, comparable to what is observed in patients with p53abn ECs. Methods: We hypothesized that objective assessment of the digitized hematoxylin and eosin (H&amp;E)-stained histopathology slides of the largest and most diverse EC subset, NSMP, could potentially identify clinical outcome outliers. As such, we developed an artificial intelligence (AI)-based image analysis model to identify the NSMP cases that had similar histopathological features to the p53abn subtype, as assessed by H&amp;E stain. We used a discovery cohort of 182 and an external validation cohort of 195 NSMP ECs. Results: Our AI-based image analysis model, based on deep convolutional neural networks, identified 21 (11.5%) out of the 182 NSMP cases with similar histopathological features as p53abn cases. We refer to these cases as ‘p53abn-like’ NSMPs. Compared to the rest of the NSMP cases, these cases had markedly inferior disease-specific survival (DSS) (10-year DSS 58.9% vs. 93.1% ( p&lt;3.44e-8)) and progression-free survival (PFS) (10-year PFS 55.1% vs. 91.4% ( p&lt;3.76e-6)). These findings were confirmed in our validation cohort, with 10.7% of the 195 patients categorized as ‘p53abn-like’ tumors with 10-year DSS of 82% vs. 51.3% ( p&lt;5.28e-5) and PFS of 89.3% vs. 56.6% (p&lt;2.15e-4). Conclusions: Utilizing an AI-based approach for histopathology image analysis, we have discovered ‘p53abn-like’ NSMPs, a novel subtype of NSMP ECs with morphological features similar to p53abn cases. ‘p53abn-like’ NSMPs exhibit similar clinical behavior as p53abn, having noticeably inferior outcome compared to the rest of the NSMP cases in two independent cohorts. These findings warrant further molecular investigation of this novel subtype of EC to identify the biological underpinning and future therapeutic strategies.
Pharmacokinetics (PK) and pharmacodynamics (PD) in First-MIND: A phase Ib, open-label, randomized study of tafasitamab (tafa) ± lenalidomide (LEN) in addition to R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Authors: David Belada, Katerina Kopeckova, Juan Miguel Bergua Burgues, Don A. Stevens, Grzegorz S. Nowakowski, Maeve Waldron-Lynch, Nira Hadar, Johannes Weirather, Charlotte Lässig, Derek Blair, Martin H. Dreyling
Journal: Journal of Clinical Oncology (2022)

e19553 Background: The combination of tafa + LEN has accelerated approval in the United States (2020) and conditional approval in Canada and Europe (2021) for R/R DLBCL in ASCT-ineligible adult pts. A tolerable safety profile for R-CHOP + tafa ± LEN in pts with newly diagnosed DLBCL in the Phase Ib First-MIND study (NCT04134936) was previously reported, with numerically superior efficacy for R-CHOP + tafa + LEN (ASH 2021; #3556). We report PK, PD, and immunogenicity of R-CHOP + tafa ± LEN in this first line setting. Methods: Eligible pts ≥18 years with treatment-naïve DLBCL, IPI 2–5, and ECOG PS 0–2 were randomized 1:1 to either six 21-day (D) cycles (C) of R-CHOP (R-CHO, D1; P, D1–5) + tafa (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafa + LEN (25 mg orally, D1–10) (Arm B). Secondary endpoints included tafa serum conc and number and percentage of pts developing anti-tafa Abs. Exploratory endpoints included natural killer (NK) cell, T-cell, and B-cell count in peripheral blood. Results: Data cut-off: 13 March 2021 for safety analysis, incl. ≥1 month follow-up after EoT visit for all pts; 15 September 2021 for efficacy. Tafa serum conc reached steady state by C3 (geometric mean trough conc: Arm A, 186.40–216.55 µg/mL; Arm B, 171.77–201.54 µg/mL) and steadily declined after treatment completion. Anti-tafa Abs were detected in 1/65 (1.5%) pts. This pt showed pre-existing tafa Abs at baseline, which decreased during treatment. Median NK cell count decreased from baseline at C1D8 but was at baseline or higher levels by EoT visit (Arm A) and C1D15 (Arm B; Table). T-cell count decreased from baseline at C1D8 in both arms but was at baseline level or higher by C1D15 (Arm A) and EoT visit (Arm B). Median B-cell count decreased from baseline to 0 cells/μL (Arm A, C1D15; Arm B, C1D8); at 6-month follow-up after EoT visit, B-cell count had recovered to measurable levels in ̃50% of pts. Conclusions: Tafa serum conc reached and maintained a therapeutic dose level in this first-line regimen and declined in line with known tafa half-life (̃16 days) after treatment completion; tafa levels were comparable between the two treatment arms. No pt developed treatment-induced or treatment-boosted anti-tafa Abs. Median NK-cell, T-cell, and B-cell counts were comparable between treatment arms in all cycles. Clinical trial information: NCT04134936. [Table: see text]
Whole-slide multispectral imaging reveals the immune subtypes of melanoma associated with the tumor microenvironment: An automated 7-color mIF assay.
Authors: Bhavika Patel, Stephanie Allen, Brittney Boldt, Noah Ramirez, Najiba Mammadova, Agnes Haggerty, Navi Mehra
Journal: Journal of Clinical Oncology (2022)

e21591 Background: Immunotherapy and precision medicine are rapidly developing approaches to cancer therapy. Biomarkers that detect the tumor and tumor microenvironment allow for the development of strategies that accelerate the advancement of treatments to enhance a patient’s immune system. Akoya’s MOTiF PD-1/PD-L1 Auto Melanoma Kit is a validated, multiplex immunoassay enabling detection of the 6 most clinically relevant immuno-oncology and spatial biomarkers: FoxP3, PD-L1, Sox10/S100, PD-1, CD8 and CD68. Methods: In this study, the MOTiF PD-1/PD-L1 panel was used to analyze the tumor microenvironment and specifically assess immune phenotypes within melanoma samples from 3 patients. This study demonstrates a fully optimized and end-to-end workflow solution for biomarker discovery in melanoma. Results: We demonstrate the utility of Akoya’s MOTiF PD-1/PD-L1 Melanoma panel kit in studying the cellular diversity while retaining spatial context. Stained slides were analyzed using the InForm and Phenoptr Reports image analysis platforms to identify phenotypes and better understand spatial relationships between cell phenotypes. The MOTiF PD-1/PD-L1 panel kit provides reproducibility across different patient samples. Conclusions: This data provides insight into the innate and adaptive immune landscape for targeted design of new immunotherapies as well as improved efficacy and reduced toxicity in the treatment of melanoma.
Assessing the impact of BCG on progression of NMIBC in the new EAU high risk and very high-risk groups
Authors: P. Gontero, J.L. Dominguez-Escrig, B.W.G. Van Rhijn, A.H. Mostafid, M. Roupret, D. Cohen, E. Comperat, F. Liedberg, J. Palou Redorta, M. Burger, S. Shariat, T. Seisen, V. Soukup, A. Masson-Lecomte, O. Capoun, M. Babjuk, R.J. Sylvester
Journal: European Urology (2022)
Brigatinib in Japanese patients (pts) with <i>ALK</i>+ NSCLC: Final results from the phase 2 J-ALTA trial.
Authors: Pingkuan Zhang, Toru Kumagai, Tatsuya Yoshida, Makoto Nishio, Ryo Toyozawa, Takashi Seto, Kazuhiko Nakagawa, Yuichiro Ohe, Nobuyuki Yamamoto, Kentarou Kudou, Takayuki Asato, Koichi Goto
Journal: Journal of Clinical Oncology (2022)

9075 Background: In previous J-ALTA (NCT03410108) analyses, brigatinib demonstrated substantial efficacy and manageable safety in pts with TKI-refractory and TKI-naive ALK+ NSCLC. We report the final J-ALTA results. Methods: J-ALTA was a single arm, multicenter, open-label study that included ALK TKI-naive and -refractory NSCLC expansion parts. The main cohort within the refractory part was a group with alectinib-refractory NSCLC. Primary endpoints: IRC-assessed confirmed ORR in the alectinib-refractory cohort; IRC-assessed 12-month PFS in the TKI-naive cohort. Secondary endpoints included confirmed ORR (IRC-assessed in the total refractory cohort; investigator-assessed in all cohorts); DoR, PFS, DCR, and iPFS by IRC; and safety. Final analyses were performed following last pt last contact. Results: A total of 104 pts were enrolled; 72 had TKI-refractory (56% female; median age, 53.0 y) and 32 had TKI-naive (53% female; median age, 60.5 y) NSCLC. As of 28 July, 2021 (last pt last contact), median follow-up was 24.2 mo in the refractory cohort (alectinib-refractory subgroup [n = 47], 23.0 mo) and 22.1 mo in the TKI-naive cohort. Confirmed ORR was 34% (95% CI: 21–49) by IRC with 16 partial responses (PR) in the alectinib-refractory cohort and 32% (21–44; 22 PR) in the total refractory cohort. In the TKI-naive cohort, IRC-assessed 24-mo PFS was 73% (90% CI: 55–85); median PFS was not mature. Additional efficacy analyses are reported in Table. TEAEs were reported in all 104 pts (most common: increased CPK, 79%; hypertension, 48%; diarrhea, 47%). Grade ≥3 TEAEs were reported in 68% and 91% of pts in the TKI-refractory and -naive cohorts, respectively; most commonly (TKI-refractory/naive) elevated CPK, 24%/50%; elevated lipase, 15%/19%; hypertension, 11%/34%. Pneumonitis was mandated to be reported as an SAE regardless of severity and was the only SAE reported in &gt; 5% of pts (refractory, n = 5 [7%; early onset, 1]; naive, n = 4 [13%; early onset, 0]). TEAEs led to dose interruption/reduction/discontinuation in 63%/31%/7% of pts in the TKI-refractory cohort and 94%/69%/0% in the TKI-naive cohort. Conclusions: Final efficacy and safety results in pts with TKI-refractory and -naive NSCLC were consistent with previous J-ALTA analyses. No new safety signals were observed in either cohort. Brigatinib demonstrated a favorable benefit-risk profile and is an important option for Japanese pts with ALK+ NSCLC regardless of TKI treatment history. Clinical trial information: NCT03410108. [Table: see text]
Economic impact of broad panel versus sequential single and narrow panel sequencing in lung cancer patients.
Authors: Alexa Hospodar, Brooke Byrd, Robert Cullum, Kevin Hastings, Taylor Teschner, Trish Brown, Shirisha Reddy, Suzanne Belinson, Joseff Schulin, Ira Klien, Emma Hovanec, Patrick Mergler, Elisea Avalos-Reyes, Kjel Andrew Johnson, Rogelio A. Brito
Journal: Journal of Clinical Oncology (2022)

e18718 Background: Recent developments in next-generation sequencing (NGS) technology have revolutionized our understanding of cancer biology and clinical research by improving diagnoses and recognizing mutations for personalized therapies. Sequential single (SS) gene testing and narrow panel sequencing (NPS) are used to select targeted therapies and precision medicine strategies for lung cancer patients. While broad panel sequencing (BPS) can identify more mutations than SS and NPS, it is more expensive. This study aims to assess the long-term cost-effectiveness of BPS vs. SS and NPS in lung cancer patients. Methods: This study will evaluate lung cancer patients undergoing biomarker testing insured by a large commercial and Medicare health plan in the United States between January 1, 2021, and May 31, 2021. The SS and NPS group consists of patients with 50 or fewer genes sequenced; the BPS group consists of those with more than 50 genes sequenced. Our primary clinical endpoint for analysis is the total cost of care defined as the allowed costs paid for all medical and pharmacy claims six months from the first gene sequencing panel. Multivariable regression analysis will assess the influence of explanatory variables on costs. Analysis will be complete February 28, 2022.
Patient, caregiver, and physician preferences for treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Mirko Vukcevic, Mallory Yung, Maliha Khan, Frederick Mark Schnell
Journal: Journal of Clinical Oncology (2022)

e18710 Background: Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) patients ineligible for transplantation face complex, preference-sensitive treatment decisions. Shared decision making (SDM) can improve patient engagement and treatment satisfaction, despite limited data on patient preferences and values in treatment decision-making, particularly for 2 nd and 3 rd -lines. We conducted a primary qualitative research study to better understand R/R DLBCL treatment decision-making in patients, caregivers, and physicians. Methods: We conducted 1-hour semi-structured interviews with 14 adult R/R DLBCL patients, 8 paired caregivers, and 8 oncologists of R/R DLBCL patients to understand perceived patient and caregiver involvement in treatment-related decisions, 2 nd and 3 rd -line preferences and goals, treatment satisfaction, and current SDM practices. We used template analysis to code transcripts from 6 a priori codes. 2 interviewers double-coded 8 interviews to ensure interrater reliability &gt; 75% and independently coded the remaining 22 interviews. Results: Patients said rapid-moving care and shock of diagnosis or failing treatment impeded individual and caregiver involvement in treatment decision-making, and thus relied on physician recommendations for 1 st line treatment. All patients felt they followed a well-established standard of care, adding to low self-efficacy for SDM in 71% of patients and 38% of caregivers. Caregivers also perceived treatment decisions as directives. While physicians believe patients should have total control over their treatment decisions, they agreed on barriers for involving patients in decision-making (i.e., limited treatment options, established standard of care, lack of patient understanding). Patients found that cumulative treatment experience shaped preferences and considerations in 2 nd and 3 rd -line treatment; 43% perceived higher autonomy over decision-making and had clearer expectations. 10 patients (71%) said their oncologists shared educational materials around treatment options, but some wanted resources to address ancillary concerns (e.g., mental health, fertility). Patients found caregivers helpful in enhancing their understanding of treatment-related discussions, and all physicians encouraged caregiver inclusion in treatment planning. 71% of patients felt satisfied with their treatment experience, but 21% would have liked a more individualized approach. Conclusions: Results suggest while 2 nd - and 3 rd -line R/R DLBCL treatment options may be limited, patient preferences and goals can be incorporated into long-term treatment planning. Opportunities for improvement include developing tailored educational materials for caregivers to establish them as trusted messengers and physician tools to support integration of patients’ lived experiences into their clinical workflow.
Racial disparities in receipt of guideline-concordant care for early-onset colorectal cancer in the U.S.
Authors: Leticia M. Nogueira, Folasade May, K. Robin Yabroff, Rebecca Siegel
Journal: Journal of Clinical Oncology (2022)

6544 Background: Early-onset colorectal cancer patients who are Black are less likely to survive than white patients, even for early-stage disease, possibly due to differences in receipt of guideline-concordant care. This study evaluated racial disparities in receipt of timely and guideline-concordant colon and rectal cancer care in a large nationwide sample. Methods: Non-Hispanic Black and white individuals aged 20-49 years newly diagnosed with colorectal cancer during 2004-2019 were selected from the National Cancer Database. Patients who received all care recommended by the National Comprehensive Cancer Network (staging, surgery, lymph node evaluation, chemotherapy, and radiotherapy) for which they were eligible according to cancer subsite and clinical and pathological TNM stage were considered guideline concordant. Demographic characteristics (age and sex), comorbidities, and health insurance coverage type were added sequentially to a series of multivariable models to estimate contribution to racial disparities in receipt of guideline-concordant care. Racial disparities in time from diagnosis date (among rectal cancer patients eligible for neoadjuvant chemotherapy) and surgery date (among colon cancer patients eligible for adjuvant chemotherapy) to date of chemotherapy initiation was evaluated using restricted mean survival time. Results: Of the 84,728 colon and 62,483 rectal cancer patients, 20.8% and 14.5% were Black, respectively. Black patients were less likely to receive guideline concordant care than white patients diagnosed with colon and rectal cancer, respectively (Table). Demographic characteristics and comorbidities combined explained less than 5% of the disparity, while health insurance coverage type explained 28.6% and 19.4% of the disparity among colon and rectal cancer patients, respectively. Restricted mean time to chemotherapy was statistically significantly longer among Black than white patients for colon (54.0 vs 48.7 days, p &lt;.001) and rectal cancers (49.6 vs 40.9 days, p &lt;.001), respectively. Conclusions: Black patients diagnosed with early-onset colorectal cancer receive worse and less timely care than their white counterparts. Differences in health insurance coverage type, a modifiable factor, were the largest identified contributor to the racial disparities in receipt of guideline-concordant care, suggesting that improved access to care could help mitigate disparities in cancer outcomes. [Table: see text]
Comparison of outward transmission potential between vaccinated and partially vaccinated or unvaccinated individuals with the SARS-CoV-2 delta variant infection
Authors: Sung Woon Kang, Ji Yeun Kim, Heedo Park, So Yun Lim, Jeonghun Kim, Seongman Bae, Jiwon Jung, Min Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Man-Seong Park, Sung-Han Kim
Journal: Journal of Infection (2022)
Multiomic approach to examining gut microbiome sampling methods in breast cancer and control subjects.
Authors: Christina Ann Nowicki, Lucille Ray, Phillip Engen, Andrea Madrigrano, Thomas R. Witt, Thomas E. Lad, Melody A. Cobleigh, Ece Mutlu
Journal: Journal of Clinical Oncology (2022)

10541 Background: It is well known that estrogen exposure is a major risk factor for breast cancer (BC). Estrogen levels can be affected by the gut microbiome through enterohepatic circulation. No studies regarding gut microbiome changes in BC have examined the colonic mucosal microbiome; and there is no data on which types of gut microbiome studies would be most relevant to the study of the microbiome in BC. Methods: We examined differences in the gut microbiome composition in BC and control subjects using the following sample types: Home-collected stool, endoscopically collected stool, and colonic biopsy samples (for all groups, n=48 total, n=24 BC, n=24 controls). Here, we used both operational taxonomic unit (OTU) and amplicon sequence variant (ASV) based approaches in QIIME2 for 16S rDNA sequencing analysis. Alpha diversity metrics (Chao1, Pielou’s Evenness, Faith PD, Shannon, and Simpson) and beta diversity metrics (Bray-Curtis, Weighted and Unweighted Unifrac) were calculated. LefSe was used to analyze differences in the abundance of various taxa between sample types. Results: Alpha and beta diversity metrics were different between the three sample types when using both OTU or ASV-based analysis, however there were some minor differences between analysis types in these samples. Comparing the 3 sample types, Actinobacteria and Firmicutes (Log10 LDA score &gt;4) were the predominant phyla in home stool samples, while Bacteroidetes and Proteobacteria (Log10 LDA score &gt;4) were higher in abundance in the colonic biopsy samples. Conclusions: Our data shows that alpha and beta diversity metrics differ between sampling methods (home-collected stool, endoscopically collected stool, and colonic biopsies) when looking at the composition of the gut microbiome in BC. Results remained the same regardless of ASV or OTU-based analysis. [Table: see text]
GCT-07. Central nervous system germ cell tumors of children in Slovakia from 2000 to 2020
Authors: Stanislava Hederova, Andrea Mocna, Estera Bublakova, Anna Ballova, Kristina Husakova, Terezia Stancokova, Ladislav Deak, Alexandra Kolenova
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Central nervous system germ cell tumors (CNS GCTs) are very heterogenous group of tumors, which are divided into two main subgroups - germinomas and non- germinomatous germ cell tumors (NGGCTs). NGGCTs consist of embryonal carcinomas, yolk sac tumors, choriocarcinomas, and teratomas - mature, immature, or with malignant transformation, as well as mixed types. CNS GCTs are rare tumors, accounting approximately for 4-5% of all brain tumors in children, with a peak of incidence between the ages of 10 and 15 years, affecting predominantly boys. METHODS: Retrospective study of a cohort of 34 patients, age 0-18 years old, with CNS germ cell tumors diagnosed and treated in one of three Slovak pediatric oncology centers over a 21-year period from 01/2000 to 12/2020. Treatment was done according to the SIOP strategy. RESULTS: Out of 34 patients 15 patients were treated in the largest center, in Bratislava and 19 patients in the remaining 2 centers. Germinomas occurred in 16 (47.1%) and non-germinomatous germ cell tumors in 18 (52.9%) patients, 7 of whom had teratomas. In our cohort, 24 patients (70.6%) survived with an average follow-up age of 8.5 years. Twenty two patients remain in the 1st remission of the disease, 2 patients got through after disease recurrence. Ten patients (29.4%) died, 9 patients due to disease progression and 1 patient due to treatment complications. CONCLUSION: The overall survival of children with CNS GCT is most dependent on the histologic subtype of the tumor. Overall survival in children with germinomas reaches 90% and with NGGCTs around 60-70%, depending on the extent of the disease. In our cohort, we have achieved 70.6% 5 year overall survival of patients.